Immune: A Journey Into the Mysterious System That Keeps You Alive

by Philipp Dettmer

Around 541 million years ago, multicellular animal life suddenly exploded and became visible. And not only that, it became more and more diverse, extremely quickly.

The farther separated two creatures are on the tree of life and still share a trait of the immune system, the older that trait must generally be.

We can learn a lot about the age of the immune system by comparing the defenses in very distantly related animals.

In the animal world, sponges, the most basic and oldest of all animals, which have existed for more than half a billion years, possess something that probably was the first primitive immune response in animals. It is called humoral immunity. “Humor,” in this context, is an ancient Greek term that means “bodily fluids.” So humoral immunity is very tiny stuff, made out of proteins, that floats through the bodily fluids outside of the cells of an animal. These proteins hurt and kill microorganisms that have no business being there.

So it probably did not take animals too long, in evolutionary terms, to get cells that did just that: Specialize in defense. This new cell-mediated immunity was a success story right from the start.

The first dedicated immune organs and cell training centers, together with the emergence of one of the most powerful principles of immunity—the ability to recognize specific enemies and quickly produce a lot of dedicated weapons against them, and then to remember them in the future!

your immune system is not really inside of you. It is you. It is an expression of your biology protecting itself and making your life possible.

But your immune system is also not a singular thing. It is a complex and interconnected collection of hundreds of bases and recruitment centers all over your body. They are connected by a superhighway, a network of vessels, similarly vast and omnipresent as your cardiovascular system. Even more, there is a dedicated immune organ in your chest, as big as a chicken wing, that gets less efficient as you age.

At its very core, the immune system is a tool to distinguish the other from the self. It does not matter if the other means to harm you or not.

The goal above all things is maintaining and establishing homeostasis: the equilibrium between all the elements and cells in the body.

To summarize, distinguishing between self and other is core, homeostasis is the goal, and there are seemingly infinite ways for it to all go wrong.

biochemistry becomes life for reasons we still do not understand. Let us zoom in to you and take a look—into your organs, through the tissue, to our most fundamental building blocks, your cells.

The total surface area of your skin is about two square yards

Your real weak points to infections are your mucous membranes—the

on average there are about 200 square yards (meters) of mucous membranes in a healthy adult (about the same as a tennis court), most of them being your lungs and your digestive tract.

The average human body is made from around forty trillion cells.

Something alive separates itself from the universe around it. It has a metabolism, meaning it takes up nutrients from the outside and gets rid of internal garbage. It responds to stimuli. It grows and it can make more of itself. Cells do all these things.

cells are biological robots, driven entirely by myriads of biochemical reactions guided by the even smaller parts they are made up from.

Your cells have “organs” that are called organelles, like the nucleus, the information center of your cell—a pretty large structure with its own protective border wall that houses your DNA, your genetic code. There are mitochondria, generators that transform food and oxygen into chemical energy that keeps your cells running.

A single human cell is filled up with dozens of millions of individual molecules. Half of them are water molecules,

The other half of your cells’ insides consists mostly of millions of proteins.

it is OK to call your cells protein robots.

They are so useful and manifold that a cell can use them for basically everything, from sending signals to constructing simple walls and structures to complex micromachines.

Proteins are made from chains of amino acids, which are tiny organic building blocks that come in twenty different varieties.

A typical protein is usually made from between 50 and 2,000 amino acids

the longest ones we know of are made from up to 30,000.

How do your cells know in which order to put amino acids to make the proteins they need? Well, this is the job of the code of life: Your DNA, a long sequence of instructions that are necessary for a living thing to be a living thing. What this means in this context is that around 1% of the DNA is made up of sequences that are building manuals for proteins, which are called Genes

the instructions on the DNA are converted into proteins in a two-step process: Special proteins read the information on the DNA string and convert it into a special messenger molecule called mRNA—basically the language that our DNA uses to communicate orders.

The mRNA molecule is then transported from the nucleus of the cell to another organelle, the protein production machinery called the ribosome. Here the mRNA molecule is read and translated into amino acids, that are then put together in the order inscribed into it.

Some of the most common proteins are extremely plentiful inside your cells, with up to half a million individual copies. Others are specialized and exist fewer than ten times in total.

Gravity is not a relevant force for things at this scale. And so, at room temperature, an average protein can move about sixteen feet (five meters) per second, in theory.

This process is called Brownian motion and it describes the random movement of molecules in a gas or fluid.

These interactions are fundamentally important for biology and are called biological pathways. Pathways are fancy words to describe a series of interactions between individual things that lead to a change in a cell.

Cells are filled up by proteins. Proteins are three-dimensional puzzle pieces. Their specific shapes enable them to fit together or interact with other proteins in specific ways. Sequences of these interactions, called pathways, cause cells to do things. This is what we mean when we say that cells are protein robots guided by biochemistry. The complex interactions between dumb and dead proteins create a less dumb and less dead cell, and the complex interactions between slightly dumb cells create the pretty smart immune system.

This phenomenon occurs all over nature, and is called emergence. It is the observation that entities have properties and abilities that their parts do not have. So an ant colony as an entity can do complex things, while the individual ant can’t.

This is sort of how everything in your body works. Your cells are nothing but bags of proteins guided by chemistry. But together these proteins form a living being that can do a lot of really sophisticated things.

All these parts form different and overlapping layers and systems, so it’s helpful to imagine them as empires and kingdoms that, in unison, defend the continent that is your body. We can organize them into two very different realms that together represent the most powerful and ingenious principles that nature found to defend your continent of flesh: The Realm of your Innate Immune System and the Realm of your Adaptive Immune System

The Realm of the Innate Immune System contains all the defenses you are born with and that can be employed mere seconds after an invasion occurs.

It has the power to tell self from other. And once it detects other it immediately springs into action. However, its weapons are not tailored to identify any specific enemy, but instead they try to be effective across a wide range of common enemies.

It does the heavy lifting and most of the actual fighting. The vast majority of your hundreds of billions of soldier and guard cells are part of your innate immune system.

If your innate immune system thinks an attack is serious enough, it has the power to activate and call the second line of defense to mobilize and join the fight.

The Realm of the Adaptive Immune System contains specialized super cells that coordinate and support your first line of defense.

The Adaptive Immune System has a specific answer for every single possible microorganism that exists on this planet right now—and for every single one that can evolve in the future. Think about how creepy that actually is.

It is the reason most diseases are only able to manifest themselves once in your life. But this knowledge and complexity come with downsides.

It starts as a blank slate and then gets progressively more powerful, only to get weaker again as you age. A weak Adaptive Immune System is one of the main reasons young and old humans are often much more likely to die from diseases than people in the middle of their lives.

To explore the different realms with the attention they deserve, the rest of this book is organized into three major parts. In part 2 we will experience an invasion that will occur through your skin and by bacteria and in part 3 we will witness a sneaky surprise attack on your mucosa by viruses. In part 4 we will then see how everything comes together and discuss specific disorders and diseases, from autoimmune to cancer.

Part 2 Catastrophic Damage

Most of the microorganisms that accidentally enter your body are dealt with rather quickly as they are simply not prepared for the body’s harsh defense measures. So the majority of the living things surrounding you are just mildly annoying to your immune system.

Your true enemies are an elite group that has found ways to overcome your defenses more effectively.

Any sort of invader that is able to give your immune system a run for its money is called a Pathogen—which appropriately means “the maker of suffering.”